ALPROLIX (Coagulation Factor IX Recombinant) Fc Fusion

ALPROLIX is a recombinant coagulation factor IX therapy used for the treatment of hemophilia B, a genetic bleeding disorder caused by a deficiency of clotting factor IX. The drug is produced by Bioverativ, a Sanofi company, and is designed to provide long-lasting protection against bleeding episodes in individuals with hemophilia B. By using a fusion protein technology that links factor IX with the Fc region of immunoglobulin G1 (IgG1), ALPROLIX extends the half-life of factor IX in the bloodstream, thereby reducing the frequency of injections needed for prophylactic treatment.

How It Works

ALPROLIX works by replacing the missing or deficient factor IX in individuals with hemophilia B, thereby restoring the normal blood clotting process. 1. **Recombinant Factor IX**: – ALPROLIX contains recombinant factor IX, a genetically engineered protein that mimics the natural factor IX found in human blood. This protein plays a crucial role in the coagulation cascade, a series of events that lead to blood clot formation. 2. **Fc Fusion Technology**: – The factor IX molecule in ALPROLIX is fused with the Fc region of immunoglobulin G1 (IgG1), a type of antibody. This fusion enhances the half-life of factor IX by allowing it to bind to the neonatal Fc receptor (FcRn), which protects it from lysosomal degradation in the liver. As a result, the factor IX stays in circulation longer, reducing the frequency of dosing required for effective bleeding prevention. 3. **Clot Formation**: – Once administered, ALPROLIX increases the level of factor IX in the blood. During bleeding episodes, activated factor IX (factor IXa) works in conjunction with activated factor VIII (factor VIIIa) to convert factor X to factor Xa. This conversion is an essential step in the coagulation cascade that ultimately leads to the formation of a stable blood clot, stopping the bleeding. 4. **Extended Interval Dosing**: – Due to its extended half-life, ALPROLIX allows for less frequent dosing schedules, making it a convenient option for prophylaxis in hemophilia B patients. This extended interval dosing can improve adherence and quality of life for patients who require regular clotting factor replacement therapy.

Indications

ALPROLIX is indicated for the treatment of:

• Hemophilia B (Congenital Factor IX Deficiency):
  • **Routine Prophylaxis**: To prevent or reduce the frequency of bleeding episodes.
  • **On-Demand Treatment**: For control and prevention of bleeding episodes.
  • **Perioperative Management**: To manage bleeding during and after surgical procedures.

Side Effects

ALPROLIX may cause various side effects, ranging from mild to severe. Some of the common and serious side effects include:

• Common Side Effects:
  • Headache
  • Dizziness
  • Nausea
  • Fatigue
  • Injection site reactions (pain, swelling, redness)
  • Joint pain
  • Fever
  • Upper respiratory tract infection
• Serious Side Effects:
  • **Hypersensitivity Reactions**: Symptoms may include rash, itching, swelling, and difficulty breathing. Severe allergic reactions can occur, and patients should seek immediate medical attention if they experience any signs of an allergic reaction.
  • **Inhibitor Development**: Patients may develop neutralizing antibodies (inhibitors) against factor IX, which can reduce the effectiveness of the treatment. Regular monitoring for inhibitors is recommended.
  • **Thromboembolic Events**: Though rare, there is a potential risk for blood clots forming in the veins or arteries, leading to conditions like deep vein thrombosis (DVT) or pulmonary embolism (PE).
  • **Renal Complications**: In patients with pre-existing kidney conditions, there may be a risk of renal complications.

Contraindications

ALPROLIX is contraindicated in the following situations:

• Hypersensitivity: Patients with known hypersensitivity to recombinant factor IX, hamster protein, or any components of the product should not use ALPROLIX.
• History of Severe Allergic Reactions: Individuals with a history of severe hypersensitivity reactions, including anaphylaxis, to factor IX products should avoid using ALPROLIX.
• Presence of Inhibitors: Patients who have developed inhibitors to factor IX may not respond adequately to ALPROLIX and should be monitored and managed accordingly.

Pricing Information

Below is a table detailing the price of ALPROLIX in various countries:

Country	Price (per vial)	Reference
United States	$3,000 – $4,000	GoodRx
Canada	CAD $4,000 – $5,000	DrugBank
United Kingdom	£2,500 – £3,500	NHS
Australia	AUD $5,000 – $6,000	PBS
Germany	€3,000 – €4,000	Apotheken Umschau

Top 5 Global Brands

In addition to ALPROLIX, several pharmaceutical companies produce coagulation factor IX products for hemophilia B. Here are some of the top global brands:

• BeneFIX (Coagulation Factor IX (Recombinant)) – Pfizer
• Rixubis (Coagulation Factor IX (Recombinant)) – Takeda
• Idelvion (Coagulation Factor IX (Recombinant), Albumin Fusion Protein) – CSL Behring
• Rebinyn (Coagulation Factor IX (Recombinant), GlycoPEGylated) – Novo Nordisk
• Mononine (Factor IX (Human)) – CSL Behring